LTBP1

Summary

LTBP1 (latent transforming growth factor beta binding protein 1, HGNC:6714) is a protein-coding gene on chromosome 2p22.3, encoding Latent-transforming growth factor beta-binding protein 1 (Q14766). Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space.

The protein encoded by this gene belongs to the family of latent TGF-beta binding proteins (LTBPs). The secretion and activation of TGF-betas is regulated by their association with latency-associated proteins and with latent TGF-beta binding proteins. The product of this gene targets latent complexes of transforming growth factor beta to the extracellular matrix, where the latent cytokine is subsequently activated by several different mechanisms. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 4052 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cutis laxa, autosomal recessive, type 2E (Strong, GenCC)
• GWAS associations: 60
• Clinical variants (ClinVar): 398 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 70
• MANE Select transcript: NM_206943

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6714
Approved symbol	LTBP1
Name	latent transforming growth factor beta binding protein 1
Location	2p22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000049323
Ensembl biotype	protein_coding
OMIM	150390
Entrez	4052

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 30 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000402934, ENST00000404525, ENST00000404816, ENST00000407925, ENST00000413303, ENST00000415140, ENST00000418533, ENST00000422669, ENST00000432635, ENST00000468091, ENST00000489740, ENST00000498013, ENST00000892677, ENST00000892678, ENST00000892679, ENST00000929160, ENST00000929161, ENST00000929162, ENST00000929163, ENST00000929164, ENST00000929165, ENST00000929166, ENST00000929167, ENST00000929168, ENST00000929169, ENST00000929170, ENST00000929171, ENST00000929172, ENST00000929173, ENST00000954822, ENST00000954823, ENST00000954824

RefSeq mRNA: 27 — MANE Select: NM_206943 NM_000627, NM_001166264, NM_001166265, NM_001166266, NM_001394905, NM_001394906, NM_001394907, NM_001394908, NM_001394909, NM_001394910, NM_001394911, NM_001394912, NM_001394913, NM_001394914, NM_001394915, NM_001394916, NM_001394917, NM_001394918, NM_001394919, NM_001394920, NM_001394921, NM_001394923, NM_001394924, NM_001394925, NM_001394926, NM_001394927, NM_206943

CCDS: CCDS33177, CCDS33178, CCDS54344, CCDS54345

Canonical transcript exons

ENST00000404816 — 34 exons

Exon	Start	End
ENSE00000744639	33361429	33361515
ENSE00000809531	33342838	33342963
ENSE00000809552	33363390	33363518
ENSE00000809554	33364216	33364356
ENSE00000809557	33257284	33257511
ENSE00000932485	33252677	33252844
ENSE00000932486	33262722	33262821
ENSE00000932488	33274965	33275090
ENSE00000932491	33280039	33280158
ENSE00000932497	33397133	33397282
ENSE00000962596	32948875	32948945
ENSE00001006668	33020909	33021206
ENSE00001006673	33259588	33259610
ENSE00001006675	33273656	33273781
ENSE00001006678	33389184	33389306
ENSE00001070241	33360597	33360779
ENSE00001070242	33365333	33365503
ENSE00001070253	33347367	33347510
ENSE00001070255	33275801	33275923
ENSE00001163417	33110582	33110751
ENSE00001550837	32946953	32947818
ENSE00001554326	33398364	33399509
ENSE00001615737	33217552	33217654
ENSE00001682704	33222080	33222151
ENSE00001745039	33188577	33188851
ENSE00002074350	33263294	33263392
ENSE00003460232	33243662	33243784
ENSE00003476406	33309434	33309556
ENSE00003503333	33301522	33301644
ENSE00003507995	33293160	33293282
ENSE00003531877	33186856	33187080
ENSE00003540951	33134793	33134960
ENSE00003579206	33315144	33315269
ENSE00003616394	33300451	33300573

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 104.8498 / max 2809.3137, expressed in 1540 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19670	77.0066	1092
19671	12.3345	868
19659	6.8313	1226
19668	3.6529	659
19669	2.2567	660
19658	1.5817	716
19672	1.1139	252
19657	0.0723	18

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	99.46	gold quality
right coronary artery	UBERON:0001625	99.35	gold quality
descending thoracic aorta	UBERON:0002345	99.34	gold quality
thoracic aorta	UBERON:0001515	99.20	gold quality
ascending aorta	UBERON:0001496	99.18	gold quality
saphenous vein	UBERON:0007318	99.17	gold quality
aorta	UBERON:0000947	99.02	gold quality
stromal cell of endometrium	CL:0002255	98.99	gold quality
urethra	UBERON:0000057	98.95	gold quality
popliteal artery	UBERON:0002250	98.90	gold quality
tibial artery	UBERON:0007610	98.89	gold quality
ventricular zone	UBERON:0003053	98.62	gold quality
coronary artery	UBERON:0001621	98.55	gold quality
left coronary artery	UBERON:0001626	98.48	gold quality
tendon of biceps brachii	UBERON:0008188	98.22	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.11	gold quality
cauda epididymis	UBERON:0004360	98.09	gold quality
periodontal ligament	UBERON:0008266	97.98	gold quality
cartilage tissue	UBERON:0002418	97.95	gold quality
tibia	UBERON:0000979	97.93	gold quality
calcaneal tendon	UBERON:0003701	97.88	gold quality
vena cava	UBERON:0004087	97.86	gold quality
decidua	UBERON:0002450	97.78	gold quality
mammalian vulva	UBERON:0000997	97.50	gold quality
smooth muscle tissue	UBERON:0001135	97.32	gold quality
visceral pleura	UBERON:0002401	97.28	gold quality
synovial joint	UBERON:0002217	97.18	gold quality
gall bladder	UBERON:0002110	97.14	gold quality
myocardium	UBERON:0002349	97.11	gold quality
mucosa of urinary bladder	UBERON:0001259	96.85	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	1146.74
E-HCAD-36	yes	1098.65
E-CURD-112	yes	40.82
E-HCAD-6	yes	20.29
E-MTAB-6678	yes	16.51
E-HCAD-10	yes	16.42
E-MTAB-5061	yes	11.42
E-CURD-119	yes	11.05
E-HCAD-11	yes	8.79
E-ENAD-27	yes	6.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, CREB1, ELF4, ESR1, HOXB2, STAT3

miRNA regulators (miRDB)

95 targeting LTBP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10523-5P	99.91	69.22	2038

Literature-anchored findings (GeneRIF, showing 40)

• Latent transforming growth factor beta-binding protein 1 interacts with fibrillin and is a microfibril-associated protein (PMID:12429738)
• The current study was carried out to understand hormonal regulation of LTBP-1 expression in normal and SV-40 virus transformed human lung fibroblasts (PMID:14626352)
• The LTBP1 protein expressed from a cDNA encoding only the TGF-beta-LAP-binding domain was incapable of supporting alphavbeta6-integrin-mediated activation. (PMID:15564041)
• The single nucleotide polymorphisms -202G/C and +20A/C on the LTBP-1L promoter may affect the clinical outcome of ovarian cancer patients, probably via up-regulating protein expression. (PMID:16825507)
• LTBP-2 specifically interacts with the amino-terminal region of fibrillin-1 and competes with LTBP-1 (PMID:17293099)
• heparan sulfate proteoglycans may play a critical role in regulating TGF-beta availability by controlling the deposition of LTBP1 into the extracellular matrix in association with fibronectin (PMID:17580303)
• MT1-MMP-mediated proteolytic processing of ECM-bound LTBP-1 is a mechanism to release latent TGF-beta from the subendothelial matrix. (PMID:18602101)
• TGFB1 as an important candidate gene for further biological studies of IgA nephropathy and as a possible target for therapy. Our data also indicate a possibility of a gender effect in the genetic background of IgA nephropathy (PMID:19258388)
• Data identify LTBP-1 as an important modulator of TGF-beta activation in glioma cells, which may contribute to the malignant phenotype. (PMID:19431147)
• codon 10 polymorphism in TGFB1 may have a significant influence on the development of PCa and BPH and that the T allele of the TGFB1 gene has a dominant effect on the development of PCa and BPH (PMID:19829035)
• TGF-beta(1) augmented Tumor necrosis factor-like weak inducer of apoptosis (TWEAK)-induced production of IL-8 and MCP-1 by retinal pigment epithelial cells. (PMID:19895311)
• TGF-beta1 gene -509C/T polymorphism was associated with severe TID. The higher value in serum concentration of TGF-beta1 was also associated with severe TID and the T T genotype/T allele. (PMID:20446778)
• extracellular HSP90beta is a negative regulator for the activation of latent TGF-beta1 modulating TGF-beta signaling in the extracellular domain. (PMID:20599762)
• large latent TGFbeta complex (LLC), which contains latent TGFbeta-binding protein 1 (LTBP-1), is directly dependent on the pericellular assembly of fibrillin microfibrils, which interact with fibronectin during higher-order fibrillogenesis. (PMID:20699357)
• Study indicates marked differences in the expression pattern of LTBP1 mRNA and protein in early lesions compared with advanced lesions. (PMID:21071877)
• A strong negative correlation between LTBP-1 and P-Smad2 immunoreactivity was found, implying that LTBP-1 is not likely to contribute directly to the increased levels of TGF-beta activity in malignant mesothelioma. (PMID:21106222)
• a spliced variant form of latent transforming growth factor beta binding protein 1, LTBPD41 is highly expressed in advanced atherosclerotic lesions (PMID:21161366)
• genetic polymorphism is associated with both lack of microfilariae and differential microfilarial loads in the blood of persons infected with lymphatic filariasis (PMID:21843572)
• results suggest that the CC genotype of the TGF-beta1 gene increases the risk to develop LOAD and is also associated with depressive symptoms in AD. (PMID:21924590)
• We have shown that TGF-beta1 expression in gastric tumor tissue with HER2/neu-negative status is of prognostic relevance in gastric cancer. (PMID:22015652)
• Force-induced latency-associated peptide conformational changes result in transforming growth factor (TGF)-beta1 release. Mechanical pulling opens the straitjacket structure that keeps TGF-beta1 latent. (PMID:22169532)
• susceptibility genes associated with alcohol drinking (PMID:22295116)
• Increased generation of reactive oxygen species (ROS) and enhanced expression of NADPH oxidases were found to be associated with the TGF-beta1-induced autophagy. (PMID:22322529)
• The expression of PAI-1 mRNA and TGF-beta1 mRNA was significantly higher in the cDNA samples obtained from the atopic cataracts than those obtained from the senile cataracts. (PMID:22410565)
• Elevated expression of either TGF-beta1 or TGF-beta2 in cells that represent the early stages in the development of human squamous cell carcinoma results in a more aggressive phenotype. (PMID:22414291)
• Data show that plasma TGF-beta1 was elevated in the circulation of patients with brain tumors and that significant decreases in TGF-beta1 levels were observed after the removal of benign and malignant tumors. (PMID:22632886)
• Dysregulated expression of TWIST1, TGF-beta1 and SMAD3 mRNA observed in osteoarthritis bone is reflected in the functionality of the osteoblast when these cells are cultured ex vivo. (PMID:22820497)
• The high incidence of intimal hyperplasia in patients with surgically repaired congenital heart disease (CHD) is correlated with TGF-beta1 expression and may contribute to the development of atherosclerotic coronary artery disease in CHD patients. (PMID:23395279)
• these results suggested that the C allele could increase TGF-beta secretion which suppresses antitumour immune responses and may affect the Oral squamous cell carcinoma risk. (PMID:23442056)
• High transforming Growth Factor beta1 expression is associated with myelofibrosis. (PMID:23462118)
• Lipocalin-2 negatively modulates the epithelial-to-mesenchymal transition in hepatocellular carcinoma through the epidermal growth factor (TGF-beta1)/Lcn2/Twist1 pathway. (PMID:23696034)
• The expression of TGF-beta1 is increased while the Smad7 expression is diminished in dendritic cell infiltration decrease in liver gastrointestinal cancer metastasis. (PMID:23998914)
• There is an increasing anti-cancer protection with increased numbers of alleles associated with higher levels of TGF-beta1 and IL-4. (PMID:24164868)
• The LTBP1 C-terminus adopts a flexible “knotted rope” structure, which may facilitate cell matrix interactions. (PMID:24489852)
• LTBP-1 showed both an accumulation and a striking co-localization with Notch3-ECD deposits suggesting specific recruitment into aggregates in brain in CADASIL. (PMID:25190493)
• Significantly higher frequency of TT genotype of transforming growth factor-Beta 1 in asthma patients was found compared to controls. (PMID:25359706)
• LTBP-1 an extracellular matrix protein and key regulator of TGF-beta bioavailability is a novel HtrA1 target.Attenuation of TGF-beta signaling caused by a lack of HtrA1-mediated LTBP-1 processing as mechanism underlying CARASIL pathogenesis. (PMID:25369932)
• This review concludes that TGF-beta1 29T/C polymorphism does not play a role in breast cancer susceptibility in overall or ethnicity-specific manner. (PMID:25374198)
• The aim of this study is to evaluate whether specific inhibition of c-Abl by siRNA can influence the transforming growth factor-beta1 (TGF-beta1)-induced fibrotic responses. (PMID:25527259)
• Combination of EGF with TGF-beta1, but not EGF or TGF-beta1 alone, caused assembly of cells to a new two-dimensional structure, being characterized by dense aggregates connected by branches of few cells. (PMID:25529149)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ltbp1	ENSDARG00000056922
mus_musculus	Ltbp1	ENSMUSG00000001870
rattus_norvegicus	Ltbp1	ENSRNOG00000033090

Paralogs (3): LTBP4 (ENSG00000090006), LTBP2 (ENSG00000119681), LTBP3 (ENSG00000168056)

Protein

Protein identifiers

Latent-transforming growth factor beta-binding protein 1 — Q14766 (reviewed: Q14766)

Alternative names: Transforming growth factor beta-1-binding protein 1

All UniProt accessions (8): C9JD84, C9JDW2, Q14766, E7EV71, H7BZ76, H7C0I7, H7C2H7, H7C4L5

UniProt curated annotations — full annotation on UniProt →

Function. Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta. Outcompeted by LRRC32/GARP for binding to LAP regulatory chain of TGF-beta.

Subunit / interactions. Interacts with TGFB1; associates via disulfide bonds with the Latency-associated peptide chain (LAP) regulatory chain of TGFB1, leading to regulate activation of TGF-beta-1. LTBP1 does not bind directly to TGF-beta-1, the active chain of TGFB1. Interacts (via C-terminal domain) with FBN1 (via N-terminal domain). Interacts with FBN2. Interacts with ADAMTSL2. Interacts with EFEMP2.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in the aorta (at protein level). Isoform Long: Expressed in fibroblasts.

Post-translational modifications. Contains hydroxylated asparagine residues. Isoform Short N-terminus is blocked. Two intrachain disulfide bonds from the TB3 domain are rearranged upon TGFB1 binding, and form interchain bonds with TGFB1 propeptide, anchoring it to the extracellular matrix. O-glycosylated on serine residues by POGLUT2 and POGLUT3.

Disease relevance. Cutis laxa, autosomal recessive, 2E (ARCL2E) [MIM:619451] A form of cutis laxa, a disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, and a general connective tissue weakness. ARCL2E patients present with cutis laxa, inguinal hernia, craniofacial dysmorphology, variable heart defects, and prominent skeletal features including craniosynostosis, short stature, brachydactyly, and syndactyly. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The 8-Cys3 region in the third TB domain mediates the interchain disulfide bond interaction with the Latency-associated peptide chain (LAP) regulatory chain of TGFB1.

Similarity. Belongs to the LTBP family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q14766-1	Long, LTBP-1L	yes
Q14766-2	Short, LTBP-1S
Q14766-3	3
Q14766-4	4
Q14766-5	5

RefSeq proteins (27): NP_000618, NP_001159736, NP_001159737, NP_001159738, NP_001381834, NP_001381835, NP_001381836, NP_001381837, NP_001381838, NP_001381839, NP_001381840, NP_001381841, NP_001381842, NP_001381843, NP_001381844, NP_001381845, NP_001381846, NP_001381847, NP_001381848, NP_001381849, NP_001381850, NP_001381852, NP_001381853, NP_001381854, NP_001381855, NP_001381856, NP_996826* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR017878	TB_dom	Domain
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR026823	cEGF	Domain
IPR036773	TB_dom_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR050751	ECM_structural_protein	Family

Pfam: PF00683, PF07645, PF12662

UniProt features (147 total): disulfide bond 62, domain 22, glycosylation site 17, sequence conflict 10, strand 7, region of interest 5, modified residue 5, splice variant 4, mutagenesis site 4, compositionally biased region 3, sequence variant 2, helix 2, signal peptide 1, chain 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1KSQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14766-F1	58.92	0.01

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 974, 1137, 1414, 1597, 1616

Disulfide bonds (62): 1349–1372, 1359–1384, 1359, 1373–1389, 1374–1401, 1384, 1471–1482, 1477–1491, 1526–1550, 1536–1562, 1551–1565, 1552–1577, 1625–1636, 1631–1645, 1666–1681, 1676–1690, 1692–1705, 191–201, 195–207, 209–218 …

Glycosylation sites (17): 347, 378, 424, 620, 647, 769, 801, 937, 1019, 1059, 1141, 1197, 1224, 1250, 1366, 1488, 1687

Mutagenesis-validated functional residues (4):

Position	Phenotype
1348	abolishes interaction with the latency-associated peptide chain (lap) regulatory chain of tgfb1; when associated with 13
1366	abolishes n-glycosylation at this site without affecting ability to interact with the latency-associated peptide chain (
1382–1385	abolishes interaction with the latency-associated peptide chain (lap) regulatory chain of tgfb1; when associated with a-
1385–1388	loss of binding to tgfb1.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-2129379	Molecules associated with elastic fibres
R-HSA-2173789	TGF-beta receptor signaling activates SMADs
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-1474244	Extracellular matrix organization
R-HSA-1566948	Elastic fibre formation
R-HSA-162582	Signal Transduction
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-9006936	Signaling by TGFB family members

MSigDB gene sets: 511 (showing top): ATF_B, FXR_IR1_Q6, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, NKX25_02, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, DITTMER_PTHLH_TARGETS_UP, MODULE_493, TATTATA_MIR374, CREBP1_Q2, RACCACAR_AML_Q6, TAL1ALPHAE47_01, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1, AAAYRNCTG_UNKNOWN

GO Biological Process (4): obsolete sequestering of TGFbeta in extracellular matrix (GO:0035583), establishment of protein localization to extracellular region (GO:0035592), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), protein localization to extracellular region (GO:0071692)

GO Molecular Function (9): transforming growth factor beta receptor activity (GO:0005024), calcium ion binding (GO:0005509), transforming growth factor beta binding (GO:0050431), microfibril binding (GO:0050436), molecular adaptor activity (GO:0060090), receptor ligand inhibitor activity (GO:0141069), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515), growth factor binding (GO:0019838)

GO Cellular Component (5): microfibril (GO:0001527), extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Metabolism of proteins	2
Elastic fibre formation	1
Signaling by TGF-beta Receptor Complex	1
Post-translational protein modification	1
Extracellular matrix organization	1
Signaling by TGFB family members	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
establishment of protein localization	1
enzyme-linked receptor protein signaling pathway	1
macromolecule localization	1
transmembrane receptor protein serine/threonine kinase activity	1
metal ion binding	1
growth factor binding	1
cytokine binding	1
extracellular matrix binding	1
molecular_function	1
receptor ligand activity	1
molecular function inhibitor activity	1
structural molecule activity	1
extracellular matrix	1
protein binding	1
elastic fiber	1
supramolecular fiber	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1
cellular_component	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

101 interactions, top by confidence:

A	B	Type	Score
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
MMP10	TIMP1	psi-mi:“MI:0914”(association)	0.530
MMP3	APOE	psi-mi:“MI:0914”(association)	0.530
KBTBD7	PLD2	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
ZFP41	LRP4	psi-mi:“MI:0914”(association)	0.530
ZNF408	LRP4	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
E6	CASK	psi-mi:“MI:0914”(association)	0.520
LTBP1	FAM20C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
LOX	LTBP1	psi-mi:“MI:0407”(direct interaction)	0.440
LTBP1	TGM2	psi-mi:“MI:0407”(direct interaction)	0.440
LTBP1	PCOLCE	psi-mi:“MI:0407”(direct interaction)	0.440
LTBP1		psi-mi:“MI:0915”(physical association)	0.370
LTBP1	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
LTBP1	TGFB1	psi-mi:“MI:0403”(colocalization)	0.350
SPHK1	TAF4	psi-mi:“MI:0914”(association)	0.350
DND1	RPSA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (114): LTBP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), IGFBP3 (Reconstituted Complex), IGFBP5 (Reconstituted Complex), LTBP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS)

ESM2 similar proteins: O08999, O35485, O35806, O43278, O89103, O95428, P13207, P23943, P35054, P49765, P49766, P59383, P97766, P98153, P98154, Q00918, Q14766, Q14767, Q16610, Q28019, Q2Q0I9, Q2TAL6, Q3U515, Q4ZHG4, Q5BIR3, Q5HZW5, Q5NRP8, Q5NRQ0, Q61508, Q61810, Q62894, Q765Z5, Q7TQH7, Q7Z4F1, Q867D0, Q86T13, Q86VZ4, Q8BH27, Q8C8N3, Q8CB67

Diamond homologs: A0A1U9VX91, A2AJ76, O08999, O43897, O57382, O57460, O75095, P13497, P35556, P98063, P98070, P98133, Q00918, Q14766, Q61555, Q62381, Q75N90, Q7KVA1, Q8C088, Q8CG19, Q8JI28, Q9DER7, Q9TV36, A2AR95, A2ARV4, A2VEC9, A4IHY6, A4QPB2, A6QNY1, B3EWY9, B3EWZ6, B3M8G0, B3NBB6, B4HVU2, B4L8V5, B4LCX4, B4MLE8, B4PD96, B4QMF4, B5DFC9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LTBP1	“up-regulates activity”	TGFB1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Elastic fibre formation	5	21.8×	6e-04
Molecules associated with elastic fibres	5	20.0×	6e-04
Extra-nuclear estrogen signaling	6	13.3×	6e-04
Extracellular matrix organization	9	7.4×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

398 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	286
Likely benign	35
Benign	13

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1184249	NM_206943.4(LTBP1):c.4844del (p.Asn1615fs)	Pathogenic
1184250	NM_206943.4(LTBP1):c.4431T>A (p.Cys1477Ter)	Pathogenic
1344546	NM_206943.4(LTBP1):c.3991dup (p.Thr1331fs)	Pathogenic
4278397	NM_206943.4(LTBP1):c.2168-1G>T	Pathogenic
1184252	NM_206943.4(LTBP1):c.1342C>T (p.Gln448Ter)	Likely pathogenic
1320250	NM_206943.4(LTBP1):c.4793_4794del (p.Glu1598fs)	Likely pathogenic
2082392	NM_206943.4(LTBP1):c.4270+2T>C	Likely pathogenic

SpliceAI

7480 predictions. Top by Δscore:

Variant	Effect	Δscore
2:33021207:G:GG	donor_gain	1.0000
2:33110581:GA:G	acceptor_gain	1.0000
2:33110750:GC:G	donor_gain	1.0000
2:33110752:G:GG	donor_gain	1.0000
2:33134778:T:A	acceptor_gain	1.0000
2:33134784:C:CA	acceptor_gain	1.0000
2:33134791:A:AG	acceptor_gain	1.0000
2:33134792:G:GA	acceptor_gain	1.0000
2:33134792:GT:G	acceptor_gain	1.0000
2:33134792:GTGA:G	acceptor_gain	1.0000
2:33134957:GTGG:G	donor_gain	1.0000
2:33134959:GG:G	donor_gain	1.0000
2:33134960:GG:G	donor_gain	1.0000
2:33134961:G:A	donor_loss	1.0000
2:33134961:G:GG	donor_gain	1.0000
2:33134962:TGAG:T	donor_loss	1.0000
2:33134963:GAGTT:G	donor_loss	1.0000
2:33186854:A:AG	acceptor_gain	1.0000
2:33186855:G:GG	acceptor_gain	1.0000
2:33186855:GT:G	acceptor_gain	1.0000
2:33186855:GTA:G	acceptor_gain	1.0000
2:33186855:GTAA:G	acceptor_gain	1.0000
2:33186855:GTAAT:G	acceptor_gain	1.0000
2:33188575:A:AG	acceptor_gain	1.0000
2:33188576:G:GG	acceptor_gain	1.0000
2:33188576:GTGA:G	acceptor_gain	1.0000
2:33188846:TCAC:T	donor_gain	1.0000
2:33220927:G:GG	donor_gain	1.0000
2:33222078:A:AG	acceptor_gain	1.0000
2:33222079:G:GA	acceptor_gain	1.0000

AlphaMissense

11345 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:32948911:G:C	W177C	1.000
2:32948911:G:T	W177C	1.000
2:33134826:T:C	F356S	1.000
2:33134826:T:G	F356C	1.000
2:33134840:T:C	C361R	1.000
2:33134904:T:C	L382P	1.000
2:33134909:A:C	S384R	1.000
2:33134911:T:A	S384R	1.000
2:33134911:T:G	S384R	1.000
2:33134951:T:C	F398L	1.000
2:33134952:T:G	F398C	1.000
2:33134953:C:A	F398L	1.000
2:33134953:C:G	F398L	1.000
2:33186861:T:A	C403S	1.000
2:33186861:T:C	C403R	1.000
2:33186862:G:A	C403Y	1.000
2:33186862:G:C	C403S	1.000
2:33186862:G:T	C403F	1.000
2:33186863:C:G	C403W	1.000
2:33186873:T:C	C407R	1.000
2:33186875:T:G	C407W	1.000
2:33186891:T:A	C413S	1.000
2:33186891:T:C	C413R	1.000
2:33186892:G:C	C413S	1.000
2:33186909:T:A	C419S	1.000
2:33186909:T:C	C419R	1.000
2:33186910:G:C	C419S	1.000
2:33186915:T:A	C421S	1.000
2:33186915:T:C	C421R	1.000
2:33186916:G:C	C421S	1.000

dbSNP variants (sampled 300 via entrez): RS1000001962 (2:32955011 G>A), RS1000002632 (2:33126348 A>C,G), RS1000006566 (2:33178426 G>A), RS1000011226 (2:33292985 C>T), RS1000015870 (2:33167783 C>A,T), RS1000019516 (2:33203902 A>T), RS1000025713 (2:33136794 A>C,G), RS1000040011 (2:33012774 G>A), RS1000058177 (2:32991172 A>T), RS1000059157 (2:33290141 T>C), RS1000061572 (2:33254102 T>C,G), RS1000062225 (2:33280765 A>C), RS1000065000 (2:32978180 TTCC>T), RS1000078344 (2:33251174 C>T), RS1000081311 (2:32996292 T>C,G)

Disease associations

OMIM: gene MIM:150390 | disease phenotypes: MIM:619451

GenCC curated gene-disease

Disease	Classification	Inheritance
cutis laxa, autosomal recessive, type 2E	Strong	Autosomal recessive

Mondo (2): cutis laxa, autosomal recessive, type 2E (MONDO:0030337), congenital heart disease (MONDO:0005453)

Orphanet (0):

HPO phenotypes

70 total (30 of 70 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000023	Inguinal hernia
HP:0000076	Vesicoureteral reflux
HP:0000179	Thick lower lip vermilion
HP:0000218	High palate
HP:0000271	Abnormality of the face
HP:0000280	Coarse facial features
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000431	Wide nasal bridge
HP:0000444	Convex nasal ridge
HP:0000455	Broad nasal tip
HP:0000494	Downslanted palpebral fissures
HP:0000520	Proptosis
HP:0000527	Long eyelashes
HP:0000767	Pectus excavatum
HP:0000929	Abnormal skull morphology
HP:0000973	Cutis laxa
HP:0001156	Brachydactyly
HP:0001159	Syndactyly
HP:0001270	Motor delay
HP:0001328	Specific learning disability
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility
HP:0001511	Intrauterine growth retardation
HP:0001582	Redundant skin
HP:0001635	Congestive heart failure
HP:0001999	Abnormal facial shape
HP:0002021	Pyloric stenosis

GWAS associations

60 associations (top):

Study	Trait	p-value
GCST000522_9	Height	7.000000e-06
GCST000611_5	Height	8.000000e-08
GCST000817_159	Height	2.000000e-09
GCST001532_9	Immune response to smallpox vaccine (IL-6)	4.000000e-08
GCST001538_1	Immune reponse to smallpox (secreted IFN-alpha)	1.000000e-07
GCST001956_31	Height	2.000000e-10
GCST002647_99	Height	2.000000e-18
GCST002702_20	Height	7.000000e-22
GCST004063_36	Waist circumference adjusted for body mass index	7.000000e-07
GCST004063_62	Waist circumference adjusted for body mass index	1.000000e-08
GCST004067_166	Hip circumference adjusted for BMI	3.000000e-07
GCST004067_224	Hip circumference adjusted for BMI	8.000000e-09
GCST004067_59	Hip circumference adjusted for BMI	6.000000e-13
GCST004500_126	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	2.000000e-07
GCST004501_109	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-07
GCST004504_81	Waist circumference adjusted for BMI in non-smokers	1.000000e-06
GCST004562_13	Waist circumference adjusted for body mass index	5.000000e-06
GCST004562_214	Waist circumference adjusted for body mass index	4.000000e-06
GCST004562_76	Waist circumference adjusted for body mass index	5.000000e-08
GCST004562_85	Waist circumference adjusted for body mass index	8.000000e-08
GCST004563_150	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-06
GCST004563_222	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-08
GCST004563_44	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-06
GCST004563_62	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	3.000000e-08
GCST004564_8	Waist circumference adjusted for BMI in active individuals	2.000000e-07
GCST004564_9	Waist circumference adjusted for BMI in active individuals	1.000000e-06
GCST005170_22	Intraocular pressure	1.000000e-10
GCST005580_134	Intraocular pressure	8.000000e-18
GCST005790_84	Rosacea symptom severity	4.000000e-07
GCST006366_14	Central corneal thickness	2.000000e-08

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004695	intraocular pressure measurement
EFO:0009180	rosacea severity measurement
EFO:0005213	central corneal thickness
EFO:0009959	diverticular disease
EFO:0004574	total cholesterol measurement
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

71 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, decreases expression	6
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	6
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	5
trichostatin A	affects cotreatment, increases expression	3
bisphenol S	decreases expression, decreases methylation, increases expression, affects cotreatment	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	3
Progesterone	increases expression, affects cotreatment	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol A	affects methylation, affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases methylation, increases mutagenesis	2
Cadmium	decreases expression, increases abundance, decreases reaction, increases expression	2
Cisplatin	affects response to substance, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
testosterone enanthate	affects expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
titanium dioxide	increases expression, affects binding	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	decreases reaction, decreases expression	1
afimoxifene	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D9IW	Ubigene HEK293 LTBP1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE